Obesity is a worldwide health epidennic and a major contributor to the increased occurrence of coronary heart disease, hypertension, fatty liver disease, and type 2 diabetes. During the past 30 years, the prevalence of overweight and obesity has increased for both adults and children in the United States. About 60 million adults, or 30% of the adult population, are now obese. It is well accepted that many factors contribute to the development of obesity and associated disorders. Both clinical research and studies in rodent models have provided key insights into the pathogenesis of obesity and associated diseases, as well as their impact on the brain. However, human and rodent studies are subject to limitations that can hamper their direct translation to effective therapeutic interventions. The nonhuman primate (NHP) has emerged as a critical model for integrating data from rodent and human studies. The overall objective of this proposal is to perform parallel physiological, genomic, and proteomic analyses in a NHP model of high-fat diet-induced obesity (DIO). The major strengths of this model are that: 1) The progression of DiO in the NHP is similar to that in humans, and this model develops the full spectrum of associated diseases;2) the experimental environment of the animals is carefully controlled so that food intake is accurately known;and 3) Extensive characterization of the metabolic phenotype of the animals is feasible. PUBLIC RELEVANCE (provided by applicant): The specific objectives of this proposal are to characterize changes in gene and protein expression levels in the hypothalamus that are associated with obesity in the NHP. While these studies are primarily descriptive and correlative, this information will provide a critical database for the general scientific community and will allow both clinical and basic scientists to generate novel specific hypothesis about systems within the brain that become dysfunctional in association with obesity. These data will also provide key insights for the future development of therapeutics for the treatment of metabolic diseases